Many proteins bind guanine nucleotides and function as regulators of many complex cellular processes (Alberts, B. et al. (1994) Molecular Biology of the Cell, Garland Publishing, Inc., New York, N.Y. pp. 206-207, 641). Exchange of bound GDP for GTP followed by hydrolysis of GTP to GDP provides a signaling mechanism that enables GTP-binding proteins to alter their conformation and interactions with other cellular components (Alberts, B. et al. (supra) pp. 207-209). GTP-binding proteins operate in a cycle that typically depends upon two auxiliary components: a guanine-nucleotide-releasing protein to catalyze the exchange of GDP for GTP and a GTPase-activating protein to trigger the hydrolysis of the bound GTP. Two structurally distinct classes of GTP-binding proteins are recognized: trimeric GTP-binding proteins (also called G proteins), consisting of three different subunits, and the monomeric GTP-binding proteins (also called monomeric GTPases), consisting of a single polypeptide chain (Alberts, B. et al. (supra) p. 641).
Members of the monomeric GTPase superfamily share a core domain with a conserved three-dimensional structure and a common GTPase cycle, but perform a wide variety of regulatory tasks in eukaryotic cells (Bourne, H. (1995) Philos. Trans. R. Soc. Lond. B. Biol. Sci. 349:283-289). Monomeric GTPases play important roles in gluconeogenesis, protein synthesis, membrane-vesicle interactions, and cytokinesis (Alberts, B. et al. (supra) pp. 85, 211, 239-240, 642-645; Mori, T. et al. (1996) Cytogenet. Cell Genet. 73:224-27).
Developmentally regulated GTP-binding protein (DRG) is present in mouse embryonic tissues, in particular the central nervous system, spleen, lung, liver, muscle, kidney and testis (1992a) Biochem. Biophys. Res. Comm. 189:371-377). DRG messenger RNA expression is down-regulated during brain development (Sazuka, T. et al. Supra). Similar DRG proteins that bind GTP have been described in embryonic Xenopus laevis and in embryonic and adult Drosophila melanogaster (Kumar, S. et al. (1993) Int. J. Dev. Biol. 37:539-546; Sommer, K. A. et al. (1994) Mol. Gen. Genet. 242:391-398). These proteins harbor an ATP/GTP-binding site motif A (P-loop; PS00017), the GTP1/OBG (GTP-binding protein) family signature (ATP/GTP-binding site motif B; PS00905) and three other GTP-interacting domains (Sazuka, T. et al. (1992b) Biochem. Biophys. Res. Comm. 189:363-370). Antibodies raised against recombinant fly DRG protein localized to the perinuclear region of human Hep2 cells and mouse 3T3 cells Sommer, K. A. et al. (supra)!.
Regulation of GTP/GDP levels in the cell by GTP-binding proteins has been implicated in a number of diseases, including atherosclerosis, hypertension, faciogenital dysplasia, oncogenesis and metastasis, heart disease, Alzheimer, cystic fibrosis, and viral infection (Meijt, J. T. (1996) Mol. Cell. Biochem. 157:31-38; Olson, M. F. (1996) J. Mol. Med. 74:563-571; Wilson, C. et al. (1988) J. Cell Biol. 107:69-77).
The discovery of a new human developmentally regulated GTP-binding protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of immune, abnormal vesicle trafficking, smooth muscle, and neoplastic disorders.